Hypoxia Promotes Gluconeogenesis Through PGC-1α in the Liver of Lasiopodomys brandtii.

Oxygen is a critical factor for the survival of most lifeforms, as inadequate availability disrupts internal metabolic balance. Hypoxia-induced disruptions in glucose metabolism can be fatal to many animals. However, there is currently limited research on the energy metabolism of species that inhabit environments with intermittently low oxygen levels. In this study, we investigated the gluconeogenic metabolic response patterns of adult Lasiopodomys brandtii (Brandt's vole) and Mus musculus (Kunming mice) under hypoxia (10% O2, 12 h), followed by 1 h reoxygenation period. Our results indicated that, unlike M. musculus, L. brandtii did not accumulate lactate after hypoxia treatment. This suggests that L. brandtii may deal with lactate accumulation caused by oxygen deficiency during hypoxia through the PGC-1α regulated gluconeogenesis pathway of the liver, which can restore the level of anaerobic glycolytic products in the liver and blood caused by hypoxia relatively quickly and ensure the stable survival of the organism in a hypoxic environment. Intriguingly, L. brandtii also did not exhibit O2 debt repayment after short-time reoxygenation. Our study revealed that liver PGC-1α regulating gluconeogenic metabolism in L. brandtii plays an important role in the maintenance of internal homeostasis of body acid-base balance under hypoxic environments, presenting a potential mechanism for the improvement of hypoxia tolerance in L. brandtii.